2[2-n-benzyl-n-(beta-chloroethyl) aminoethyl] pyridine and the acid salts thereof



Patented Dec. 12, 1950 UNITED STATES T OFFICE 2,533,243 ZIZ-N-BENZYL-N-(B-CHLO'RGETHYL) AMI- NOETHYL] PYRIDINE AND SALTS THEREOF THE ACID NDrawing. Application October 29, 1949, Serial No. 124,482

1 Claim.

This invention relates to novel aromatic haloamines and salts thereof.

Our novel chemicals include Z-[Z-N-benzyl- N-(fl-chloroethyl)aminoethyl] pyridine, and salts thereof with acids.

In general, the novel salts of this invention may be prepared byreacting an equivalent amount of inorganic or organic acids with thecorresponding amines, preferably in some cases under anhydrous orsubstantially anhydrous conditions. The amines may be prepared byreacting the corresponding hydro-halides with at least an equivalentamount of alkaline material, such as, for example potassium carbonate.The hydrohalides may be prepared in general by reacting thebeta-alcohols of the amines with thionyl chloride or hydrogen bromide.

The new salts of this invention are crystalline solids under usualatmospheric conditions and in general are soluble in alcohols andglycols, difiicultly soluble in water and insoluble in ether andhydrocarbons. The new amines are in general high boiling liquids,varying in color from waterwhite to yellow. They are not soluble inwater, but dissolve in ethyl alcohol, propylene glycol, and organicsolvents generally.

Our novel chemical compounds exhibit unexpected and desirable medicinalproperties, for example, as sympatholytic and adrenolytic agents. Fortherapeutic purposes these novel compounds may be administered orally orparenterally, and may be employed as tablets or in capsules or in solutons. In addition to their therapeutic properties our novel compounds areuseful in organic chem cal synthesis.

While our invent on comprehends salts of the amines set forth above andacids in general, we prefer to employ those acids having an ionizationconstant of at least about 1 at normal room temperature (about 25 0.).Examples of some suitable organic acids are picric, trichloroacetic,oxalic and maleic acids. Examples of some suitable inorganic acids arehydrochloric, hydrobromic, sulfuric, phospheric (first hydrogen),perchloric, nitric and iodic acids.

In order to illustrate this invention more fully but without therebylimiting it, the following examples are given.

EXAMPLE 1 PREPARATION or 2-[2-N-BENzYL-N-(pi-Chrono- ETHYL AMINOETHYL1PYRIDINE DIHYDROCHLO RIDE (a) Preparation of Z-(2-chloroethyl) pyridinehydrochloride A solution of 360 g. of thionyl chloride in 300 cc. ofchloroform was dropped during 3 hours into a mixture of 360 g. of2-(2-hydrOxyethyD- pyridine in 200 cc. of chloroform being stirred andcooled in an ice-bath. Stirring was then continued for 6 hours; nextmorning, the chloroform was distilled off. The resinous residue wasdried for one hour in vacuo (4 mm.) at C. Repeated trituration of theresin with petroleum ether yielded a solid which was recrystallized fromisopropanol in the presence of decolorizing carbon. Slightly brownish,very hygroscopic crystals (210 g.) which melted at about 120 C. wereobtained.

Calcd. for Cvl-leNClz: 01-, 20.0; total o1,

39.9. Found: Cl, 20.5; total Cl, 39.6.

(b) Z-EZ-N-benzyl N (c hydrorethyl) aminoethyl] pyridine Sixty g. of2-(2-chloroethyl)-pyridine hydrochloride were added during 25 minutes to150 g. of 2-benzylarninoethanol being stirred and heated to C. Themixture was then heated to C. for 6 hours. After cooling to roomtemperature a solution of 40 g. of sodium hydroxide in 200 cc. of waterwas added and the formed amino alcohol extracted with 200 cc. ofbenzene. The benzene solution was washed with 300 cc. of water and driedwith anhydrous sodium sulfate. A brown oil resulted after filtrationfrom the salt and removal of the solvent. 38 g. of the desired aminoalcohol were obtained as slightly yellow oil by vacuum distillation; B.P. (5 mm.) 198- 202 C.; TL 2o=1.55O0.

Anal. Calcd. for Ciel-N202 C, 75.0; H, 7.8; N.

10.9. Found: C, 74.4; H, 7.4; N, 10.7.

Anal.

(0) 2- [2-N-beneyZ-N- (c-chloroethyl) aminoethyl] pyridinedihydrochlorz'de Twenty-five g. of thionyl chloride dissolved in 100 cc.of chloroform were dropped during two hours into a solution of 33 g. ofthe amino alcohol (b) in 100 cc. of chloroform being stirred and cooledin an ice-bath. Stirring was continued for 5 hours at 10 C. and for 12hours at room temperature. The solvent was then removed by distillationat diminished pressure; 20 cc. of absolute alcohol were added to theresidue and distilled off in vacuo. A solid was formed which wasrefluxed with 100 cc. of absolute alcohol in the presence of a smallamount of decolorizing carbon. The filtered solution was mixed with 15cc. of a saturated solution of hydrogen chloride in alcohol and 200 cc.of ether. Crystallization in the refrigerator yielded smeary crystalswhich became well-defined after tritura- 3 tion with absolute ether.Three recrystallizations from absolute alcohol and ether (150-200 cc. ofeach solvent) yielded 10 g. of the desired substance in form of slightlybrownish crystals; M. P. 171-172".

Anal. Calcd. for C1eH21N2C13: Cl, 20.4; total 01-,

20.4; total C], 30.6. Found: 01-, 20.3; total 01, 30.5.

The foregoing illustrates the practice of this invention, which however,is not to be limited 4 thereby but is to be construed as broadly aspermissible in view of the prior art and limited solely by the appendedclaim.

We claim: 2-[2-N-benzyl-N- (B chloroethyl) aminoethyl] pyridinedihydrochloride.

WILLIAM S. GUMP. EDWARD JOSEPH NIKAWITZ.

No references cited.

Certificate of Correction Patent N 0. 2,533,243 December 12, 1950WILLIAM S.GUMP ET AL.

It is hereby certified that error appears in the printed specificationof the above numbered patent requiring correction as follows:

Column 2, line 1, for 360 g. read 369 9.; column 3, lines 6 and 7, forCI, 20.4; total Cl, 20.4; total CI, 30.6 read OZ, 20.4; total UZ 30.6;

and that the said Letters Patent should be read as corrected above, sothat the same may conform to the record of the case in the PatentOfiice. Signed and sealed this 13th day of February, A. D. 1951.

THOMAS F. MURPHY,

Assistant Commissioner of Patents.

